PFI-2 hydrochloride is a a first-in-class, potent, highly selective, and cell-active inhibitor of the methyltransferase activity of SETD7 with IC50 of 2 nM, 500 fold active than (S)-PFI-2.IC50 value: 2 nM [1]Target: SETD7(R)-PFI-2 is highly selective (>1,000-fold) for SETD7, over a panel of 18 other human protein methyltransferases and DNMT1, and was shown to be inactive against 134 additional ion channel, GPCR, and enzyme targets (<35% inhibition at 10 μM). (R)-PFI-2 binds to SETD7 only in the presence of SAM. PFI-766, a biotinylated variant of (R)-PFI-2 that retains the ability to bind and inhibit SETD7 (IC50 110 ± 26 nM in our in vitro enzymatic assay). PFI-766 engagement of endogenous SETD7 was also confirmed by mass spectrometry that supported the high specificity of the compound for endogenous SETD7.
References:
[1]. Barsyte-Lovejoy D, et al. (R)-PFI-2 is a potent and selective inhibitor of SETD7 methyltransferase activity in cells. Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):12853-8.